Elevated circulating branched chain amino acids are an early event in pancreatic adenocarcinoma development
View/ Open
Author
Mayers, Jared R.
Clish, Clary B.
Torrence, Margaret E.
Fiske, Brian P.
Yuan, Chen
Bao, Ying
Davidson, Shawn M.
Papagiannakopoulos, Thales
Yang, Annan
Dayton, Talya L.
Qian, Zhi Rong
Cochrane, Barbara B.
Liu, Simin
Wactawski–Wende, Jean
Pollak, Michael N.
Kimmelman, Alec C.
Souza, Amanda
Pierce, Kerry
Wang, Thomas J.
Heiden, Matthew G. Vander
Wolpin, Brian M.
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1038/nm.3686Metadata
Show full item recordCitation
Mayers, J. R., C. Wu, C. B. Clish, P. Kraft, M. E. Torrence, B. P. Fiske, C. Yuan, et al. 2014. “Elevated circulating branched chain amino acids are an early event in pancreatic adenocarcinoma development.” Nature medicine 20 (10): 1193-1198. doi:10.1038/nm.3686. http://dx.doi.org/10.1038/nm.3686.Abstract
Most patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with advanced disease and survive less than 12 months1. PDAC has been linked with obesity and glucose intolerance2-4, but whether changes in circulating metabolites are associated with early cancer progression is unknown. To better understand metabolic derangements associated with early disease, we profiled metabolites in prediagnostic plasma from pancreatic cancer cases and matched controls from four prospective cohort studies. We find that elevated plasma levels of branched chain amino acids (BCAAs) are associated with a greater than 2–fold increased risk of future pancreatic cancer diagnosis. This elevated risk was independent of known predisposing factors, with the strongest association observed among subjects with samples collected 2 to 5 years prior to diagnosis when occult disease is likely present. We show that plasma BCAAs are also elevated in mice with early stage pancreatic cancers driven by mutant Kras expression, and that breakdown of tissue protein accounts for the increase in plasma BCAAs that accompanies early stage disease. Together, these findings suggest that increased whole–body protein breakdown is an early event in development of PDAC.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191991/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:15034814
Collections
- HMS Scholarly Articles [17922]
- SPH Scholarly Articles [6362]
Contact administrator regarding this item (to report mistakes or request changes)